Automated analysis of three-dimensional stress echocardiography

Real-time three-dimensional (3D) ultrasound imaging has been proposed as an alternative for two-dimensional stress echocardiography for assessing myocardial dysfunction and underlying coronary artery disease. Analysis of 3D stress echocardiography is no simple task and requires considerable expertise. In this paper, we propose methods for automated analysis, which may provide a more objective and accurate diagnosis. Expert knowledge is incorporated via statistical modelling of patient data. Methods for identifying anatomical views, detecting endocardial borders, and classification of wall motion are described and shown to provide favourable results. We also present software developed especially for analysis of 3D stress echocardiography in clinical practice. Interobserver agreement in wall motion scoring is better using the dedicated software (96%) than commercially available software not dedicated for this purpose (79%). The developed tools may provide useful quantitative and objective parameters to assist the clinical expert in the diagnosis of left ventricular function.     

Effect of Alpha Linolenic Acid Supplementation on Serum Prostate Specific Antigen (PSA): Results from the Alpha Omega Trial

Background

Alpha linolenic acid (ALA) is the major omega-3 fatty acid in the diet. Evidence on health effects of ALA is not conclusive, but some observational studies found an increased risk of prostate cancer with higher intake of ALA. We examined the effect of ALA supplementation on serum concentrations of prostate-specific antigen (PSA), a biomarker for prostate cancer.

Methods

The Alpha Omega Trial (ClinicalTrials.gov Identifier: {"type":"clinical-trial","attrs":{"text":"NCT00127452","term_id":"NCT00127452"}}NCT00127452) was a double-blind, placebo-controlled trial of ALA and the fish fatty acids eicosapentanoic acid (EPA) and docosahexanoic acid (DHA) on the recurrence of cardiovascular disease, using a 2×2 factorial design. Blood was collected at the start and the end of the intervention period. The present analysis included 1622 patients with a history of a myocardial infarction, aged 60–80 years with an initial PSA concentration <4 ng/mL. They received either 2 g per day of ALA or placebo in margarine spreads for 40 months. T-tests and logistic regression were used to assess the effects of ALA supplementation on changes in serum PSA (both continuously and as a dichotomous outcome, cut-off point: >4 ng/mL).

Findings

Mean serum PSA increased by 0.42 ng/mL on placebo (n = 815) and by 0.52 ng/mL on ALA (n = 807), a difference of 0.10 (95% confidence interval: −0.02 to 0.22) ng/mL (P = 0·12). The odds ratio for PSA rising above 4 ng/mL on ALA versus placebo was 1.15 (95% CI: 0.84–1.58).

Interpretation

An additional amount of 2 g of ALA per day increased PSA by 0.10 ng/mL, but the confidence interval ranged from −0.02 to 0.22 ng/mL and included no effect. Therefore, more studies are needed to establish whether or not ALA intake has a clinically significant effect on PSA or prostate cancer.

Trial registration information

ClinicalTrials.gov; Identifier: {"type":"clinical-trial","attrs":{"text":"NCT00127452","term_id":"NCT00127452"}}NCT00127452. URL: http://www.clinicaltrials.gov/ct2/show/{"type":"clinical-trial","attrs":{"text":"NCT00127452","term_id":"NCT00127452"}}NCT00127452.     

Differential response of cycling and noncycling cells to inducers of DNA synthesis and mitosis

The objective of this study was to determine whether cells in G(0) phase are functionally distinct from those in G(1) with regard to their ability to respond to the inducers of DNA synthesis and to retard the cell cycle traverse of the G(2) component after fusion. Synchronized populations of HeLa cells in G(1) and human diploid fibroblasts in G(1) and G(0) phases were separately fused using UV-inactivated Sendai virus with HeLa cells prelabeled with [(3)H]ThdR and synchronized in S or G(2) phases. The kinetics of initiation of DNA synthesis in the nuclei of G(0) and G(1) cells residing in G(0)/S and G(1)/S dikaryons, respectively, were studied as a function of time after fusion. In the G(0)/G(2) and G(1)/G(2) fusions, the rate of entry into mitosis of the heterophasic binucleate cells was monitored in the presence of Colcemid. The effects of protein synthesis inhibition in the G(1) cells, and the UV irradiation of G(0) cells before fusion, on the rate of entry of the G(2) component into mitosis were also studied. The results of this study indicate that DNA synthesis can be induced in G(0)nuclei after fusion between G(0)- and S-phase cells, but G(0) nuclei are much slower than G(1) nuclei in responding to the inducers of DNA synthesis because the chromatin of G(0) cells is more condensed than it is in G(1) cells. A more interesting observation resulting from this study is that G(0) cells is more condensed than it is in G(1) cells. A more interesting observation resulting from this study is that G(0) cells differ from G(1) cells with regard to their effects on the cell cycle progression of the G(2) nucleus into mitosis. This difference between G(0) and G(1) cells appears to depend on certain factors, probably nonhistone proteins, present in G(1) cells but absent in G(0) cells. These factors can be induced in G(0) cells by UV irradiation and inhibited in G(1) cells by cycloheximide treatment.     

Levels and trends in cardiovascular risk factors and drug treatment in 4837 elderly Dutch myocardial infarction patients between 2002 and 2006

Background

It is important to gain insight into opportunities for secondary prevention of cardiovascular disease. Our aim was to investigate levels and trends in cardiovascular risk factors and drug treatment in Dutch post-myocardial infarction (MI) patients between 2002 and 2006 and to make comparisons with the EUROASPIRE surveys (1999–2007).

Methods

We analysed data from 4837 post-MI patients (aged 69 years, 78% men) from 32 Dutch hospitals, using baseline cross-sectional data from the Alpha Omega Trial.

Results

Between 2002 and 2006, significant declines were found in the prevalence of smoking (23% to 16%, p < 0.001), hypercholesterolaemia (≥5 mmol/l; 54% to 27%, p < 0.0001) and hypertension (≥140/90 mmHg; 58% to 48%, p < 0.001). The prevalence of antithrombotic drugs was high (97%). The prevalence of lipid-modifying drugs and antihypertensives was high, and increased (74% to 90%, p < 0.0001 and 82% to 93%, p < 0.001, respectively). The prevalence of obesity (27%) was high in 2002 and decreased to 24% in 2006, albeit not significantly. Diabetes prevalence was high and increased between 2002 and 2006 (18% to 22%, p = 0.02). In comparison with EUROASPIRE patients, who were on average 8–10 years younger, our study in 2006 included patients with lower levels of obesity, hypertension, hypercholesterolaemia, diabetes and lower use of antiplatelets and β-blockers, but similar levels of lipid-modifying drugs.

Conclusions

This study showed that older Dutch post-MI patients were adequately treated with drugs, and that risk factors reached lower levels than in the younger EUROASPIRE patients. However, there is room for improvement in diet and lifestyle, given the high prevalence of smoking, obesity, and diabetes.

Electronic supplementary material

The online version of this article (doi:10.1007/s12471-012-0248-z) contains supplementary material, which is available to authorized users.     

Isocitrate dehydrogenase 1 R132C mutation occurs exclusively in microsatellite stable colorectal cancers with the CpG island methylator phenotype

The CpG Island Methylator Phenotype (CIMP) is fundamental to an important subset of colorectal cancer; however, its cause is unknown. CIMP is associated with microsatellite instability but is also found in BRAF mutant microsatellite stable cancers that are associated with poor prognosis. The isocitrate dehydrogenase 1 (IDH1) gene causes CIMP in glioma due to an activating mutation that produces the 2-hydroxyglutarate oncometabolite. We therefore examined IDH1 alteration as a potential cause of CIMP in colorectal cancer. The IDH1 mutational hotspot was screened in 86 CIMP-positive and 80 CIMP-negative cancers. The entire coding sequence was examined in 81 CIMP-positive colorectal cancers. Forty-seven cancers varying by CIMP-status and IDH1 mutation status were examined using Illumina 450K DNA methylation microarrays. The R132C IDH1 mutation was detected in 4/166 cancers. All IDH1 mutations were in CIMP cancers that were BRAF mutant and microsatellite stable (4/45, 8.9%). Unsupervised hierarchical cluster analysis identified an IDH1 mutation-like methylation signature in approximately half of the CIMP-positive cancers. IDH1 mutation appears to cause CIMP in a small proportion of BRAF mutant, microsatellite stable colorectal cancers. This study provides a precedent that a single gene mutation may cause CIMP in colorectal cancer, and that this will be associated with a specific epigenetic signature and clinicopathological features.     

Cardiac rehabilitation in patients who underwent primary percutaneous coronary intervention for acute myocardial infarction: determinants of programme participation and completion

Background

Hospital length of stay after acute myocardial infarction (AMI) treated with primary percutaneous coronary intervention (pPCI) has reduced, resulting in more limited patient education during admission. Therefore, systematic participation in cardiac rehabilitation (CR) has become more essential. We aimed to identify patient-related factors that are associated with participation in and completion of a CR programme.

Methods

We identified 3,871 consecutive AMI patients who underwent pPCI between 2003 and 2011. These patients were linked to the database of Capri CR, which provides dedicated, multi-disciplinary CR. ‘Participation’ was defined as registration at Capri CR within 6 months after pPCI. CR was ‘complete’ if a patient undertook the final exercise test.

Results

In total, 1,497 patients (39%) were registered at Capri CR. Factors independently associated with CR participation included age (<50 vs. >70 year: odds ratio (OR) 7.0, 95% confidence interval (CI) 5.1–9.6), gender (men vs. women: OR 1.9, 95% CI 1.3–1.8), index diagnosis (ST-elevation myocardial infarction [STEMI] vs. non-ST-elevation myocardial infarction [NSTEMI]: OR 2.4, 95% CI 2.0–2.7) and socio-economic status (high vs. low: OR 2.0, 95% CI 1.6–2.5). The model based on these factors discriminated well (c-index 0.75). CR programme completion was 80% and was inversely related with diabetes, current smoking and previous MI. The discrimination of the model based on these factors was poor (c-index 0.59).

Conclusions

Only a minority of AMI/pPCI patients participated in a CR programme. Completion rates, however, were better. Increased physician and patient awareness of the benefits of CR are still needed, with focus on the elderly, women and patients with low socio-economic status.

     

Survival Rate and Enzyme Activities ofLactobacillus acidophilusFollowing Frozen Storage

The ability of two strains of Lactobacillus acidophilus, CRL 640 and CRL 800, to survive and retain their biological activities under frozen storage was determined. Freezing and thawing, as well as frozen storage, damaged the cell membrane, rendering the microorganisms sensitive to sodium chloride and bile salts. Both lactic acid production and proteolytic activity were depressed after 21 days at -20 degreesC, whereas beta-galactosidase activity per cell unit was increased. Cell injury was partially overcome after repair in a salt-rich medium. Copyright 1998 Academic Press.     

OPTImal CArdiac REhabilitation (OPTICARE) following Acute Coronary Syndromes: Rationale and design of a randomised, controlled trial to investigate the benefits of expanded educational and behavioural intervention programs

The majority of cardiac rehabilitation (CR) referrals consist of patients who have survived an acute coronary syndrome (ACS). Although major changes have been implemented in ACS treatment since the 1980s, which highly influenced mortality and morbidity, CR programs have barely changed and only few data are available on the optimal CR format in these patients. We postulated that standard CR programs followed by relatively brief maintenance programs and booster sessions, including behavioural techniques and focusing on incorporating lifestyle changes into daily life, can improve long-term adherence to lifestyle modifications. These strategies might result in improved (cardiac) mortality and morbidity in a cost-effective fashion. In the OPTImal CArdiac REhabilitation (OPTICARE) trial we will assess the effects of two advanced and extended CR programs that are designed to stimulate permanent adaption of a heart-healthy lifestyle, compared with current standard CR, in ACS patients. We will study the effects in terms of cardiac risk profile, levels of daily physical activity, quality of life and health care consumption.     

Reclassification of aortic stenosis by fusion of echocardiography and computed tomography in low-gradient aortic stenosis

Netherlands Heart Journal - The integration of computed tomography (CT)-derived left ventricular outflow tract area into the echocardiography-derived continuity equation results in the...